POS0671 IMPACT OF RACE ON THE EFFICACY AND SAFETY OF TOFACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS: A POST HOC ANALYSIS OF PHASE 2, 3 AND 3B/4 CLINICAL TRIALS
Authors: G. C. Wright, E. Mysler, Y. H. Chen, C. Kinch, A. Yndestad, K. Kwok, M. J. Cadatal, R. Germino, A. Ogdie
Journal: Annals of the Rheumatic Diseases (2022)

Background While racial disparities in clinical outcomes for rheumatoid arthritis (RA) patients (pts) have been described, 1 there is a paucity of data on racial differences in response to advanced therapies. Objectives To evaluate impact of self-reported race on tofacitinib efficacy/safety in RA pts. Methods This post hoc analysis used pooled data from 8 Phase (P)2, 6 P3 and 1 P3b/4 randomised controlled trials (RCTs) of RA pts treated with tofacitinib 5 or 10 mg twice daily (BID), adalimumab (ADA; 40 mg once every 2 weeks) or placebo (PBO), stratified by self-reported pt race (White, Black, Asian, Other) at baseline (BL). Efficacy outcomes (Month [M]3): ACR20/50/70 and CDAI/DAS28-4(ESR) low disease activity (LDA; scores ≤10 and ≤3.2, respectively) rates, and least squares (LS) mean change from BL (Δ) in DAS28-4(ESR) and HAQ-DI. Incidence rates (IRs; unique pts with events/100 pt-yrs) were estimated for adverse events (AEs) and serious AEs. Results 6355 pts were included (White, n=4145; Black, n=213; Asian, n=1348; Other, n=649). BL characteristics were generally similar across treatment/racial groups, excepting higher prior bDMARD exposure rates in White/Black vs Asian/Other pts. Across treatments, White, Black, Asian and Other pts most commonly enrolled from Europe (40.9%), North America (68.1%), East/South Asia (97.9%) and Latin America (80.6%), respectively; most Other pts self-reported as Hispanic and/or Latino (52.4%), followed by mixed race (36.8%) and unspecified (4.6%). At M3, ACR50 rates were higher in Other vs White pts with tofacitinib, similar across racial groups with ADA, and numerically higher in Black vs White/Asian/Other pts with PBO (Figure 1); broadly similar trends were seen with ACR20/70 and CDAI LDA rates (data not shown [DNS]). DAS28-4(ESR) LDA rates, and LS mean ΔDAS28-4(ESR) and ΔHAQ-DI were generally comparable across racial groups with active treatment, and numerically higher in Black vs White/Asian/Other pts with PBO (DNS). Across efficacy outcomes, PBO-adjusted response rates and improvements generally supported the trends observed with active treatments (Figure 1; DNS). Safety outcomes were broadly similar across treatment arms, with some higher IRs for AEs observed with Black/Other vs White/Asian pts (Table 1). Results should be interpreted with caution due to low pt numbers in some groups and the heterogenous nature of the Other pts group. Table 1. AEs and SAEs, stratified by race White Black Asian Other n IR (95% CI) n IR (95% CI) n IR (95% CI) n IR (95% CI) Tofacitinib 5 mg BID N=1699; PY=1588.3 N=93; PY=81.8 N=560; PY=548.8 N=257; PY=245.9 AE 1150 141.9 76 244.1 382 150.0 205 227.1 (133.8, 150.3) (192.4, 305.6) (135.4, 165.9) (197.1, 260.4) SAE 146 9.1 15 19.1 61 11.3 17 6.7 (7.7, 10.7) (10.7, 31.4) (8.6, 14.5) (3.9, 10.8) Tofacitinib 10 mg BID N=1264; PY=1175.4 N=60; PY=49.8 N=462; PY=487.2 N=238; PY=239.8 AE 919 188.5 48 434.3 338 178.4 190 234.3 (176.5, 201.1) (320.2, 575.8) (159.9, 198.5) (202.2, 270.1) SAE 103 8.9 2 3.9 47 9.7 15 6.2 (7.3, 10.8) (0.5, 14.3) (7.1, 12.9) (3.5, 10.2) ADA N=484; PY=390.4 N=22; PY=18.6 N=73; PY=60.1 N=64; PY=49.5 AE 318 140.4 16 162.2 51 157.0 44 161.6 (125.4, 156.7) (92.7, 263.4) (116.9, 206.5) (117.4, 216.9) SAE 31 7.6 2 10.3 9 14.5 1 1.9 (5.2, 10.8) (1.3, 37.4) (6.6, 27.5) (0.1, 10.4) PBO N=698; PY=177.3 N=38; PY=10.0 N=253; PY=72.3 N=90; PY=24.5 AE 369 311.6 23 424.9 122 251.5 48 271.4 (280.6, 345.1) (269.4, 637.6) (208.9, 300.3) (200.1, 359.8) SAE 23 12.5 1 9.4 8 10.9 3 11.5 (7.9, 18.7) (0.2, 52.2) (4.7, 21.4) (2.4, 33.6) n, number of pts with events; PY, pt-yrs; SAE, serious AE Conclusion Across racial groups, tofacitinib efficacy/safety was consistent with previous tofacitinib RA clinical programme findings. Some racial differences in clinical outcomes were observed, which may reflect regional practice norms or demographic differences. Future analyses should focus on the impact of socioeconomic, cultural, genetic or practice-based differences that may underpin these results. References [1]Greenberg et al. Am J Med 2013; 126: 1089-1098. Acknowledgements Study sponsored by Pfizer Inc. Medical writing support was provided by Kirsten Woollcott, CMC Connect, and funded by Pfizer Inc. Disclosure of Interests Grace C. Wright Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Myriad Autoimmune, Novartis and UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Myriad Autoimmune, Novartis, Pfizer Inc and UCB, Employee of: Association of Women in Rheumatology, United Rheumatology, Eduardo Mysler Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, Roche and Sanofi, Grant/research support from: Eli Lilly, Pfizer Inc and Roche, Yi-Hsing Chen Grant/research support from: Bristol-Myers Squibb, GSK and Pfizer Inc, Cassandra Kinch Shareholder of: Pfizer Inc, Employee of: Pfizer Canada ULC, Arne Yndestad Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Kenneth Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Mary Jane Cadatal Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rebecca Germino Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Alexis Ogdie Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, CorEvitas, Eli Lilly, Gilead Sciences, GSK, Janssen, Novartis, Pfizer Inc and UCB, Grant/research support from: AbbVie, Amgen, Novartis and Pfizer Inc